False-negative Examinations Research Articles

Effect of Estrogen Replacement Therapy on the Specificity and Sensitivity of Screening Mammography

Previous studies have demonstrated that mammographic breast density increases following the initiation of estrogen replacement therapy (ERT). The effect, if any, that this increase in density has on the specificity (related to false-positive readings) and the sensitivity (related to false-negative readings) of screening mammography is unknown. Using a retrospective cohort study design, we assessed the effects of ERT on the specificity and the sensitivity of screening mammography. Participants (n = 8779) were postmenopausal women, aged 50 years or older, who were enrolled in a health maintenance organization located in western Washington state and who entered a breast cancer screening program between January 1988 and June 1993. Two-view mammography was performed as part of a comprehensive breast cancer screening visit. Menopausal status, as well as demographic and risk-factor information, was recorded via self-administered questionnaires. Hormonal replacement therapy type and use were determined from questionnaire data and from an automated review of pharmacy records. Individuals diagnosed with breast cancer within 12 months of their first screening-program mammograms were identified through use of a regional cancer registry. Risk ratios (RRs) plus 95% confidence intervals (CIs) of false-positive as well as false-negative examinations among current and former ERT users (with never users as the reference group) were calculated. Reported P values are two-sided. The specificity of mammographic screening was lower for current users of ERT than for never users or former users. Defining a positive mammographic reading as any non-normal reading (either suspicious for cancer or indeterminate), the adjusted RR (95% CI) of a false-positive reading for current users versus never users was 1.33 (1.15-1.54) (P < .001); for former users versus never users, the RR (95% CI) was 1.00 (0.87-1.15). The adjusted mammographic specificities (95% CIs) for never users, former users, and current users of ERT were 86% (84%-88%), 86% (84%-87%), and 82% (80%-84%), respectively. Defining a positive reading more rigorously (i.e., as suspicious for cancer only), the adjusted RRs (95% CIs) of false-positive readings for current users and former users (versus never users) were 1.71 (1.37-2.14) (P < .001) and 1.16 (0.93-1.45), respectively. Sensitivity was also lower in women currently receiving ERT. The unadjusted RR (95% CI) of a false-negative reading for current users versus never users was 5.23 (1.09-25.02) (P = .04); for former users versus never users, the RR (95% CI) was 1.06 (0.10-10.87). The unadjusted mammographic sensitivities (95% CI) for never users, former users, and current users of ERT were 94% (80%-99%), 94% (69%-99%), and 69% (38%-91%), respectively. Current use of ERT is associated with lower specificity and lower sensitivity of screening mammography. Lower specificity could increase the cost of breast cancer screening, and lower sensitivity may decrease its effectiveness.

Non-invasive screening for renal artery stenosis with ultrasound contrast enhancement

Our aim was to evaluate duplex ultrasound imaging in the identification of renal artery stenosis using a new technique to enhance the recorded Doppler signal. Colour Doppler studies of interlobar renal arteries were performed before and after enhancement using an intravenous contrast of galactose microparticle suspension containing microbubbles (Levovist, Schering) in patients with angiographically confirmed renal artery stenosis. Blood Pressure Unit, St. George's Hospital Medical School, and Department of Radiology. The Middlesex Hospital, London, UK. Twenty-one consecutive hypertensive patients in whom the diagnosis of renal artery stenosis was made on digital subtraction angiography. The diagnosis of haemodynamically significant renal artery stenosis (> or = 60% on angiography). With Levovist, there was a 20 db increase in the Doppler intensity and, as a result, intrarenal signals were much more clearly delineated and distinct spectral waveforms were obtained from all but one kidney, which was occluded. Significant associations were found between the degree of stenosis (as assessed by angiography) and the following Doppler parameters: diastolic velocity (F = 7.6; P < 0.01), acceleration time (F = 33.5, < 0.0001), peak systolic velocity (F = 37.7, P < 0.0001) and acceleration (F = 60.0; P < 0.0001). Without enhancement, there were five false-positive and two false-negative examinations (sensitivity 85%; specificity 79%) using the acceleration cut-off value of 3.5 m/s2 to identify haemodynamically significant renal artery stenosis (> or = 60% on angiography). After contrast enhancement, there were only three false-positive and one false-negative examinations (sensitivity 94% and specificity of 88%) using the acceleration cut-off value of 3.75 m/s2 and the examination time was reduced by approximately half (sensitivity and specificity of 90% using the acceleration cut-off value of 3.5 m/s2). Our results suggest that renal duplex scanning using contrast enhancement is a promising new non-invasive technique in screening patients with suspected renal artery stenosis. Contrast enhancement produces more reproducible spectral waveforms, improves accuracy and halves the examination time.

Spontaneous vertebral dissection: clinical, conventional angiographic, CT, and MR findings.

The purpose of this study was to determine if typical clinical and neuroradiologic patterns exist in patients with spontaneous vertebral artery (VA) dissection. The medical records and neuroradiologic examinations of 14 patients with spontaneous VA dissection were reviewed. The medical records were examined to exclude patients with a history of trauma and to record evidence of a nontraumatic precipitating event ("trivial trauma") and presence of possible risk factors such as hypertension. All patients underwent conventional angiography, 13 either CT or MRI (11 both CT and MRI), and 3 MRA. Conventional arteriograms were evaluated for dissection site, evidence of fibromuscular dysplasia, luminal stenosis or occlusion, and pseudoaneurysm formation. CT examinations for the presence of infarction or subarachnoid hemorrhage. MR examinations for the presence of infarction or arterial signal abnormality, and MR angiograms for abnormality of the arterial signal column. Seven patients had precipitating events within 24 h of onset of symptoms that may have been causative of dissection and five had hypertension. At catheter angiography, two patients had dissections in two arteries (both VAs in one patient, VA and internal carotid artery in one patient), giving a total of 15 VAs with dissection. Dissection sites included V1 in four patients, V2 in one patient, V3 in three patients, V4 in six patients, and both V3 and V4 in one patient. Luminal stenosis was present in 13 VAs, occlusion in 2, pseudoaneurysm in 1, and evidence of fibromuscular dysplasia in 1. Posterior circulation infarcts were found on CT or MR in five patients. Subarachnoid hemorrhage was found on CT in two patients and by lumbar puncture alone in two patients. Abnormal periarterial signal on MRI was seen in three patients. MRA demonstrated absent VA signal in one patient, pseudoaneurysm in one, and a false-negative examination in one. Repeat catheter angiography of nine VAs at an interval ranging from 2 weeks to 1 year showed progression to occlusion in two arteries, unchanged appearance in 4, and angiographic resolution in three, which did not closely correlate with clinical outcome. No preferred site of dissection along the course of the VA was found in this study. CT and MR examinations of the head are frequently normal in patients with VA dissections. No correlation between clinical outcome and findings at repeat angiography was demonstrated.

Intestinal malrotation in children: tutorial on radiographic diagnosis in difficult cases.

To analyze difficult diagnostic cases of malrotation to identify features crucial to accurate diagnosis. The authors reviewed the radiographs and records of 81 symptomatic children who underwent surgery with a preoperative diagnosis of malrotation. Eleven had subtle rotational abnormalities (potential false-negative examinations), and 12 had false-positive upper gastrointestinal examinations. Subtle signs of malrotation included unusual redundancy of the duodenum to the right of the spine and location of the duodenojejunal junction (DJJ) medial to the left pedicle. Nevertheless, two children with variations of malrotation had normal upper gastrointestinal examinations. False-positive diagnoses resulted from failure to recognize normal variants: jejunum in the right upper quadrant as the sole finding, DJJ over the left pedicle on the anteroposterior view, "duodenum inversum," and "duodenum mobile." Three children had bowel distention that displaced the DJJ. Diagnosis of difficult cases of malrotation may depend on recognition of anatomic subtleties. False-positive diagnoses may be avoided by appreciation of normal duodenal variants.

Flexible endoscopy for the diagnosis of esophageal trauma.

The role of flexible endoscopy in the diagnosis of esophageal trauma remains undefined. This study evaluates the use of immediate flexible fiberoptic esophagogastroduodenoscopy (EGD) as the primary diagnostic tool for detection of esophageal injury in trauma patients. Flexible EGD was performed on 31 patients for this purpose from August 1991 through January 1994. There were 28 males and 3 females with a mean age of 24.3 years (range, 16-54 years). Twenty-four of 31 patients (77%) were intubated at the time of the examination. Mechanism of injury was penetrating in 24 patients (20 gunshot wounds, four stab wounds) and blunt (motor vehicle crash) in seven patients. Penetrating injuries were located in the neck in 5 of 24 patients, in the chest in 15 of 24 patients, and in both the neck and chest in 4 of 24 patients. Upper gastrointestinal contrast studies were performed for 3 of 31 patients (10%), computed tomography was performed for eight patients (26%), bronchoscopy was performed for 13 patients (42%), angiography was performed for 17 patients (55%), and rigid esophagoscopy and laryngoscopy were each performed for one patient (3%). Evidence of esophageal trauma during EGD was seen in 5 of 31 patients. True-positive studies occurred for four patients, false-positive results occurred for one patient, true-negative results occurred for 26 patients (as demonstrated by exploration in five and clinical follow-up in 21), and no false-negative examinations occurred. Sensitivity of flexible EGD was 100%, specificity was 96%, and accuracy was 97%. No complications occurred related to the performance of EGD. Flexible fiberoptic endoscopy seems to be a safe and effective method for both detection and exclusion of esophageal trauma.

Pelvic and perineal complications of Crohn's disease: assessment using magnetic resonance imaging.

This study evaluated the role of magnetic resonance imaging (MRI) in the demonstration of the pelvic and perianal complications of Crohn's disease. Twenty five patients with active Crohn's disease were studied (12 male; mean age 41.1 years). MRI examinations were performed using a 1.5 Tesla system, within 14 days after clinical assessment. T1 and T2 weighted fast spin echo sequences in two or three orthogonal planes were performed, with fat suppression in some cases. The MRI results were correlated with surgical and clinical findings. In 16 patients, cutaneous, deep perineal or enterovesical fistulas or abscesses were diagnosed at MRI which showed close correlation with findings at examination under anaesthetic. In eight patients no fistulas or abscesses were seen at MRI nor was there any evidence of complications on clinical examination and flexible sigmoidoscopy. There was one false negative examination in a patient who had a colovesical fistula. In conclusion, MRI can accurately show the pelvic and perineal complications of Crohn's disease and may render examination under anaesthetic unnecessary.

Usefulness of Magnetic Resonance Imaging for the Diagnosis of Acute Musculoskeletal Infections in Children

Summary: A 30-month prospective study was conducted on 43 children who presented with clinical findings suggestive of acute hematogenous musculoskeletal infection. Magnctic rcsonancc imaging (MRI) was found to be ex-tremely sensitive (0.97) and specific (0.92) in helping to diagnose these infections, with only one false positive and one false negative study. Bone scans are more likely to yield false positive and negative examinations. MRI is particularly useful in difficult cases in which there are conflicting clinical data or infection involving the spine or pelvis. After MRI demonstrates the location of the discase proccss, histologic and/or bacteriologic confirmation of the etiology is still mandatory.

Usefulness of Magnetic Resonance Imaging for the Diagnosis of Acute Musculoskeletal Infections in Children

A 30-month prospective study was conducted on 43 children who presented with clinical findings suggestive of acute hematogenous musculoskeletal infection. Magnetic resonance imaging (MRI) was found to be extremely sensitive (0.97) and specific (0.92) in helping to diagnose these infections, with only one false positive and one false negative study. Bone scans are more likely to yield false positive and negative examinations. MRI is particularly useful in difficult cases in which there are conflicting clinical data or infection involving the spine or pelvis. After MRI demonstrates the location of the disease process, histologic and/or bacteriologic confirmation of the etiology is still mandatory.

Evaluation of possible interference of anti-inflammatory drugs upon scintigraphic imaging with macrophage targeting 99mTc-J001X: Effects of methylprednisolone, dexamethasone, indomethacin and methotrexate

J001X, an acylated poly-(1,3)-galactoside isolated from Klebsiella pneumoniae proteoglycan, has been developed to target cells from the monocyte-macrophage lineage. Recent experimental work and initial clinical trials have proved the potential of this molecule labeled with 99mTc for the scintigraphy of inflammatory foci. In a model of radiation-induced inflammation in pigs, the scintigraphic contrast was observed to be very sensitive to a single injection of methylprednisolone given 12 h before scintigraphy. The present study was undertaken to confirm this effect and to estimate the possible interference of various anti-inflammatory agents on the in vivo targeting of macrophages by J001X. Methylprednisolone, dexamethasone, indomethacin and methotrexate used at an immunosuppressive dose were tested to assess the possible risk of false-negative examinations in patients thus treated. Analysis of the results indicated that among the four drugs tested, only methylprednisolone at 0.5–1 mg/kg could interfere with J001X scintigraphy.

Radiology of biliary complications following paediatric liver transplantation

Biliary complications (BC) are well recognised following paediatric liver transplantation. We reviewed retrospectively 169 consecutive liver transplants performed in 139 children. BC occurred in 36/169 grafts (21 %) in 35/139 patients (25 %). Biliary obstruction was present in 18/169 grafts (11 %), biliary leakage in 14/169 grafts (8 %) and a combination of obstruction and leakage was present in 4/169 (2 %) grafts. BC were as likely to present radiologically as they were with either clinical and/or biochemical abnormalities. Most BC (26/36, i. e. 72 %) occurred in the first 2 weeks following transplantation. Ultrasound and cholangiography were the principle imaging modalities used for detection of these complications. False negative ultrasound examinations occurred in three patients with biliary obstruction and in three patients with biliary leakage. False negative cholangiograms occurred in two patients with biliary leakage. Ultrasound is important in the post-operative surveillance of paediatric liver transplants, with cholangiography having a complementary role in those with BC.

Transabdominal ultrasonography as the primary investigation in patients with suspected crohn's disease or recurrence: A prospective study

Traditionally, patients with suspected or known and possible recurrent Crohn's disease have been investigated by small bowel barium radiology, which incurs a relatively high radiation dose. Despite patient selection a significant number have a normal barium examination. A prospective study was performed to evaluate the use of transabdominal ultrasound as the initial investigation in these two groups. One hundred and twenty-seven patients were examined, including 31 with a previous history of Crohn's disease. In the known Crohn's disease group there were 14 true positive ultrasound examinations and eight true negative, with six false positive and three false negative examinations. In the 96 patients not previously known to have Crohn's disease, there were 18 true positive and 70 true negative examinations, with two false positive and six false negative examinations. The overall sensitivity for ultrasound was 78% with a specificity of 91%. A significant learning curve was apparent in the early stages of study; in the last 64 patients the sensitivity was increased to 87%. These data support the use of ultrasound as the initial investigation in patients with suspected Crohn's disease or recurrence, prior to consideration for small bowel barium radiology, to reduce the large number of unnecessary small bowel barium examinations currently being performed.

Ultrasonographically guided fine needle aspiration cytology and core-needle biopsy in the diagnosis of breast tumors

The present study was designed to assess the performance of fine needle aspiration cytology (FNAC) and core-needle biopsy (CNB) of breast lesions when these procedures are performed under sonographic guidance. The results obtained in 1142 FNAC procedures and 180 CNB procedures were analysed. The study took place in a University Hospital and a private practice clinic. The patients eligible for this study were a series of women, in whom at least one hypoechoic, limited mass was found at breast ultrasonography. Cystic masses were excluded from the study. Each individual mass was investigated using either FNAC or CNB under sonographic guidance. Accuracy characteristics to suspect or diagnose malignant and pre-malignant breast lesions, such as sensitivity and specificity, were calculated. The cytological results were classified into four categories according to standard criteria: benign; atypical and/or suspiscious for cancer (hyperplasia with atypia); malignant; and unsatisfactory for diagnosis specimen. Tissue specimens were classified according to the W.H.O. The 1142 lesions submitted to FNAC included 66 invasive carcinomas, 4 intraductal carcinomas, and 4 atypical hyperplasias. FNAC led to 6 false-negative examinations, equally distributed between small (volume ≤ 1 cm 3), and larger lesions, and 1 false-positive examination. There were 12.9% ( 147 1142 ) inadequate smears. Only 3 inadequate samples were obtained in the presence of a discrete pathologic lesion (3/363, or 0.1%). All 3 corresponded to invasive carcinomas. The majority of inadequate samples ( 144 147 , or 98.0%) were obtained in the normal/dystrophic group. Overall, the sensitivity is 92.1%, and the specificity is 84.8%. The 180 lesions submitted to CNB included 31 invasive carcinomas, 5 intraductal carcinomas, and 17 atypical hyperplasias. CNB, in this series, had an accuracy rate of 100%. In conclusion, US guidance increases the accuracy of breast tissue sampling procedures. This is of particular importance as the number of suspicious images to be investigated steadily increases, as the result of mass screening.

Treatment and treatment results of mouth floor cancers

The records of 68 patients with cancer of the floor of the mouth were reviewed. 56 patients underwent surgical management, 51 of them got additionally postoperative radiation. The tumour-specific five years' survival for patients with operation was 46%, 57% of treatment failures developed from local recurrence of the tumour. In 52% of all cases there was a spread to the lymphatic system in the histological evaluation. There was high incidence of false negative clinical examinations of the neck. Conservative neck dissection was the procedure of choice for clinically positive lymph nodes and for the elective management of the neck. Only advanced tumours showed involvement of the mandibular bone. Therefore a conservative management of mandibular resection was preferred. Radical tumour extirpation and histological controlling with serial sectioned specimens are methods of avoiding local tumour recurrence.

An audit of ultrasound diagnosis of gallbladder calculi.

Many series suggest that ultrasound is an accurate method for demonstrating cholelithiasis. However, these series were often prospective and the examinations performed by experienced sonographers. This audit addresses whether the accuracy is maintained in daily practice. We reviewed the ultrasound scans of 128 patients who underwent cholecystectomy for cholelithiasis and compared the findings. The operative and ultrasound findings were at variance in eight of the 128 patients (6.2%). Five were reported as having gallstones on ultrasound but none were found at cholecystectomy, a false positive rate for ultrasound of 3.9%. Three had abnormal gallbladders with no gallstones on ultrasound but gallstones were found at operation, a false negative rate of 2.3%. To avoid false positive diagnoses, suboptimal examinations should be repeated and the scan should be repeated immediately pre-operatively if only small calculi are seen. Alternative imaging should be performed if necessary, either cholescintigraphy in the acute situation or elective oral cholecystography. Some false negative examinations may be avoided by performing repeat examinations if the gallbladder is thick-walled and tender. With these provisos we conclude that ultrasound correctly diagnoses cholelithiasis in daily practice.

Computed tomography of primary transitional cell carcinoma of upper urinary tracts

Preoperative computed tomography (CT) was utilized to evaluate 20 patients with primary transitional cell carcinoma of the upper urinary tracts. Of the 20 patients, 18 (90 %) had CT visualization of the tumor as either a discrete mass or local ureteral and/or renal pelvic wall thickening; 2 (10 % ) had false-negative examinations. Seven of the 20 patients (35 %) had CT evidence of tumor extension demonstrated by frank tumor invasion beyond the urothelium or by perirenal pelvic and/or periureteral fat streaks. Of the 4 patients with fat streaks, 2 (50 %) had superficial tumors (T AT 2), 1 had a T, (25 %) tumor, and 1 had a T3 (25 %) tumor. All 3 patients with CT findings of direct extension of tumor through the wall of the ureter or renal pelvis had T3 tumors. Among the 13 with localized noninvasive tumor on CT, 5 (38 %) had superficial tumors (T A, TIS, T 1), 5 (38 %) had T2 tumors, and 3 (21 %) had T3 tumors. Of the 5 patients with enlarged regional lymph nodes (≥1.5 cm) on CT, 2 had tumor confirmed histologically, 2 had subsequent negative CT-guided biopsies, and 1 had a negative lymphadenectomy. Distant metastasis was discovered in 1 patient. The data suggest that when CT demonstrates direct tumor extension through the renal pelvic or ureteral wall, it is a sensitive indicator of high-stage disease. However, in the absence of this finding, CT is of limited value in staging patients with primary transitional cell carcinoma of the pyeloureteral system.

Influence of CT on Tumor Classification of Laryngeal Carcinomas

The routine use of CT in 51 consecutive patients with squamous cell carcinoma of the larynx revealed cartilage involvement or extra-laryngeal tumor growth consistent with a T4 tumor which made 14 patients candidates for laryngectomy. Only 5 of these had a T4 classification by clinical examination while 8 cases were upstaged from T3. Except for one supraglottic tumor upstaged from T2 to T4, CT did not change the classification for T1 and T2 tumors, Whose localization was mainly glottic, and there were 2 false-negative examinations. It is concluded that CT is mandatory only in advanced tumors of the glottic region or when the anterior commissure is involved. However, in suspected malignancies of the sub- or supraglottic regions CT should always be carried out because these patients are at an increased risk of unexpected deep tumor growth.

Acute appendicitis confined to the appendiceal tip: evaluation with graded compression sonography.

Focal appendicitis at the tip of the appendix has not been emphasized in the sonographic literature. We present the sonographic findings in four patients with pathologically confirmed acute appendicitis confined to the appendiceal tip. In all four patients, the base of the appendix had a normal appearance with maximal outer diameters measuring 4 to 6 mm. However, the inflamed tip was focally enlarged, measuring greater than 7 mm. The importance of a careful survey of the entire length of the appendix is emphasized to avoid a false-negative examination.

Influence of CT on Tumor Classification of Laryngeal Carcinomas

The routine use of CT in 51 consecutive patients with squamous cell carcinoma of the larynx revealed cartilage involvement or extralaryngeal tumor growth consistent with a T4 tumor which made 14 patients candidates for laryngectomy. Only 5 of these had a T4 classification by clinical examination while 8 cases were upstaged from T3. Except for one supraglottic tumor upstaged from T2 to T4, CT did not change the classification for T1 and T2 tumors, whose localization was mainly glottic, and there were 2 false-negative examinations. It is concluded that CT is mandatory only in advanced tumors of the glottic region or when the anterior commissure is involved. However, in suspected malignancies of the sub- or supraglottic regions CT should always be carried out because these patients are at an increased risk of unexpected deep tumor growth.

Hidden damage revealed.

Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal lesions should be suspected when a patient receiving NSAID therapy has pain or signs of hemorrhage that are severe enough to warrant an emergency endoscopy. However, with endoscopy, patients receiving NSAID therapy with no particular gastrointestinal symptoms may also be found to have lesions. These lesions are polymorphic in character and lack clear anatomic and clinical parallels with spontaneous lesions. Endoscopically, they are of three types: (1) Advanced focal or diffuse lesions, uncommon and not usually seen in ambulatory patients; (2) large or diffuse, ulcerated or hemorrhagic lesions, that can be differentiated from those seen in typical digestive system pathology; and (3) microlesions, often responsible for false-negative examinations and now detectable through advances in electronic endoscopy. Lower bowel or ileocolonic damage is also a common finding but has only recently come to clinical attention. The endoscopic appearance of these intestinal lesions suggests a superficial inflammatory bowel disease such as hemorrhagic rectocolitis or Crohn's disease.

Perivalvular pseudoaneurysm complicating bacterial endocarditis: MR detection in five cases.

Bacterial endocarditis usually affects the valve leaflets, but erosion into the valve anulus and adjacent myocardium may form a myocardial abscess. Perivalvular abscesses can drain into the ventricles or aorta, forming a life-threatening pseudoaneurysm. We reviewed our experience with cardiac MR imaging of this disorder. Fourteen patients with complicated bacterial endocarditis underwent ECG-gated spin-echo cardiac MR imaging in addition to conventional duplex two-dimensional echocardiography (2-D echo). Angiography was performed in seven patients, six of whom underwent surgery for valve replacement. MR imaging detected the pseudoaneurysms in all five of the surgically proved cases, while 2-D echo detected only three. Clinical follow-up suggested there were no false-negative examinations, but no autopsy data were available for confirmation. Postoperative MR imaging studies were conducted in three patients, revealing two recurrent pseudoaneurysms and one thrombosed aneurysm. Cardiac MR imaging provides useful pre- and postoperative information in patients with perivalvular pseudoaneurysms due to endocarditis.